The pathogenesis of alcoholic pancreatitis remains obscure. Three major hypotheses have been proposed: 1) pancreatitis results from direst toxic damage caused by alcohol or its metabolities such as acetaldehyde; 2) alcoholism increases duodeno-pancreatic reflux, and 3) chronic alcoholism causes changes in the character of pancreatic secretion resulting in protein plugs and stones that obstruct pancreatic ducts. None of these hypotheses seem to satisfactorily explain the underlying mechanisms that cause pancreatitis in alcoholics. We reason that in the light of recent developments in pancreatic physiology and experimental pancreatitis, another approach to this problem could be taken. In experimental pancreatitis induced by either choline-deficient diet or supramaximal stimulation, the most prominent and common features are enhancement of pancreatic enzyme synthesis and some inhibition of the zymogen exocytosis. As a result, secretory enzymes either fuse with lysosomal enzymes in vacuoles (crynophagia) or are released to the cytoplasm and interstitium. We postulate that a similar basic mechanism may be present in alcoholic pancreatitis. To investigate this we propose first, to analyze the effect of alcohol ingestion in the form of common alcoholic beverages ion the release of GI peptides, CCK, secretin. gastrin and PP and on pancreatic exocrine secretion. For this sampling of the duodenal content after alcoholic beverages in fasting and after a meal will be done. Healthy volunteers, chronic alcoholics and patients with alcoholic pancreatitis will be studied. In addition, synthesis of pancreatic enzymes will be assessed by measuring incorporation of selenium-75-labelled methionine into the proteins of duodenal aspirates. Second, we propose to analyze the events that take place in the pancreas of animals after alcohol ingestion. Specially, we will study the acute effect of alcohol on CCK-stimulated pancreatic hydrolases and lysosomal enzyme secretion in a perfused rabbit pancreas preparation. Release of these enzymes into the protal blood will also be measured. To gain some insight in the fate of pancreatic enzymes ultrastructural changes in the acinar cell will be sought in the rat pancreas after acute and chronic alcohol treatment.